GALIPDIA study: Reaching lipid targets in a population with type 2 diabetes (T2DM) from the Northwest of Spain.

AIM: To assess the degree of compliance with the European ESC/EAS 2016 and 2019 dyslipidaemia guidelines in patients with type 2 diabetes mellitus (T2DM). METHODS: Multicentre retrospective cross-sectional study, conducted in 380 adults with T2DM and dyslipidaemia in 7 Spanish health areas. INCLUSION CRITERIA: minimum follow-up of one year in Endocrinology Units, at least one visit in 2020 and a lipid profile measurement in the last 3 months. EXCLUSION CRITERIA: familial hypercholesterolaemia, recent hospitalisation, active oncological pathology and dialysis. RESULTS: According to the 2016 and 2019 guidelines the majority of patients were classified as being at very high cardiovascular risk (86.8% vs. 72.1%, respectively). LDL-c compliance was adequate in 62.1% of patients according to the 2016 guidelines and 39.7% according to the 2019 guidelines (p<0.001). Clinical conditions such as history of cardiovascular disease and therapy-related aspects (use of statins, especially high-potency statins, combination therapies and good adherence) were significantly associated with greater achievement of lipid targets. CONCLUSION: There is a discrepancy between dyslipidaemia guideline recommendations and the reality of lipid control in patients with T2DM, despite most of these patients being at very high cardiovascular risk. Strategies to optimise lipid-lowering treatments need to be implemented.

Ghrelin in obesity, physiological and pharmacological considerations.

The aim of this review is to summarize the physiological and pharmacological aspects of ghrelin. Obesity can be defined as an excess of body fat and is associated with significant disturbances in metabolic and endocrine function. Obesity has become a worldwide epidemic. In obesity there is a decreased growth hormone (GH) secretion, and the altered somatotroph secretion in obesity is functional. Ghrelin is a peptide that has a unique structure with 28 amino-acids and an n-octanoyl ester at its third serine residue, which is essential for its potent stimulatory activity on somatotroph secretion. The pathophysiological mechanism responsible for GH hyposecretion in obesity is probably multifactorial, and there is probably a defect in ghrelin secretion. Ghrelin is the only known circulating orexigenic factor, and has been found to be reduced in obese humans. Ghrelin levels in blood decrease during periods of feeding. Due to its orexigenic and metabolic effects, ghrelin has a potential benefit in antagonizing protein breakdown and weight loss in catabolic conditions such as cancer cachexia, renal and cardiac disease, and age-related frailty. Theoretically ghrelin receptor antagonists could be employed as anti-obesity drugs, blocking the orexigenic signal. By blocking the constitutive receptor activity, inverse agonists of the ghrelin receptor may lower the set-point for hunger, and could be used for the treatment of obesity. In summary, ghrelin secretion is reduced in obesity, and could be partly responsible for GH hyposecretion in obesity, ghrelin antagonist or partial inverse agonists should be considered for the treatment of obesity.

Función endocrina en la obesidad / Endocrine function in obesity

La obesidad se asocia con importantes anomalías en la función endocrina. La hiper insulinemia y la resistencia a la insulina son las dos alteraciones mejor conocidas, aunque sus mecanismos y su significado clínico no están claros. El tejido adiposo se considera un órgano endocrino con secreción hormonal; el aumento en la secreción de leptina, una señal de saciedad, por el adipocito es una alteración característica. En la obesidad hay una disminución en la secreción de hormona de crecimiento; esta alteración en la función somatotropa de la obesidad es funcional y se puede revertir en determinadas circunstancias. El mecanismo fisiopatológico responsable de la hiposecreción de GH en la obesidad es probablemente multifactorial. Existen muchos datos que sugieren que un estado crónico de hipersecreción de somatostatina resulta en una inhibición de la liberación de GH; el aumento de los ácidos grasos libres probablemente contribuye a esta alteración, así como un déficit en la secreción de ghrelina. En mujeres, la obesidad abdominal se asocia a hiperandrogenismo y a niveles disminuidos de proteína transportadora de hormonas sexuales. Los hombres obesos tienen niveles de testosterona y concentraciones de gonadotropinas disminuidos, especialmente en los casos de obesidad mórbida. La obesidad se asocia con un aumento en la tasa de producción de cortisol, que se compensa con un aumento del aclaramiento del mismo, lo cual resulta en niveles plasmáticos de cortisol libre que no se modifican con el aumento del peso corporal. Ghrelina es el único factor orexígeno circulante conocido y se ha visto que se encuentra disminuido en humanos obesos. En la obesidad hay también una tendencia a aumentar las concentraciones de TSH y T3 libre (AU)

Obesity is associated to significant disturbances in endocrine function. Hyper insulinemiaand insulin resistance are the best known changes in obesity, but their mechanisms andclinical significance are not clearly established. Adipose tissue is considered to be a hormonesecretingendocrine organ; and increased leptin secretion from the adipocyte, a satiety signal, is a well-established endocrine change in obesity. In obesity there is a decreased GH secretion.Impairment of somatotropic function in obesity is functional and may be reversed in certaincircumstances. The pathophysiological mechanism responsible for low GH secretion in obesityis probably multifactorial. There are many data suggesting that a chronic state of somatostatinhypersecretion results in inhibition of GH release. Increased FFA levels, as well as a deficientghrelin secretion, probably contribute to the impaired GH secretion. In women, abdominalobesity is associated to hyperandrogenism and low sex hormone-binding globulin levels. Obesemen, particularly those with morbid obesity, have decreased testosterone and gonadotropinlevels. Obesity is associated to an increased cortisol production rate, which is compensated forby a higher cortisol clearance, resulting in plasma free cortisol levels that do not change whenbody weight increases. Ghrelin is the only known circulating orexigenic factor, and has beenfound to be decreased in obese people. In obesity there is also a trend to increased TSH andfree T3 levels (AU)

[Endocrine function in obesity]. / Función endocrina en la obesidad.

Obesity is associated to significant disturbances in endocrine function. Hyper insulinemia and insulin resistance are the best known changes in obesity, but their mechanisms and clinical significance are not clearly established. Adipose tissue is considered to be a hormone-secreting endocrine organ; and increased leptin secretion from the adipocyte, a satiety signal, is a well-established endocrine change in obesity. In obesity there is a decreased GH secretion. Impairment of somatotropic function in obesity is functional and may be reversed in certain circumstances. The pathophysiological mechanism responsible for low GH secretion in obesity is probably multifactorial. There are many data suggesting that a chronic state of somatostatin hypersecretion results in inhibition of GH release. Increased FFA levels, as well as a deficient ghrelin secretion, probably contribute to the impaired GH secretion. In women, abdominal obesity is associated to hyperandrogenism and low sex hormone-binding globulin levels. Obese men, particularly those with morbid obesity, have decreased testosterone and gonadotropin levels. Obesity is associated to an increased cortisol production rate, which is compensated for by a higher cortisol clearance, resulting in plasma free cortisol levels that do not change when body weight increases. Ghrelin is the only known circulating orexigenic factor, and has been found to be decreased in obese people. In obesity there is also a trend to increased TSH and free T3 levels.

Marked GH secretion after ghrelin alone or combined with GH-releasing hormone (GHRH) in obese patients.

OBJECTIVES: Ghrelin is a 28-amino-acid peptide, predominantly produced by the stomach. It displays a strong GH-releasing activity mediated by the hypothalamus-pituitary GH secretagogue (GHS)-receptor (GHS-R). There are different studies that suggest the importance of ghrelin in feeding and weight homeostasis. In obesity there is a markedly decreased GH secretion. For both children and adults, the greater the body mass index (BMI), the lower the GH response to provocative stimuli, including the response to GHRH. However, the response to the natural GH secretaogogue ghrelin is unclear at the present time. The aim of the present study was to evaluate the GH response to ghrelin alone or combined with GHRH in a group of obese patients, in order to further understand the deranged GH secretory mechanisms in obesity and to clarify the mechanism of action of ghrelin. PATIENTS AND MEASUREMENTS: Six obese female patients (31 +/- 3.4 years) with a BMI of 36.1 +/- 7.7 kg/m(2) were studied. As a control group, six normal nonobese female subjects of similar age and sex were studied. Four tests were performed: placebo, GHRH [1 micro g/kg, no more than 100 micro g, intravenous (i.v.)], ghrelin (1 micro g/kg, no more than 100 micro g, i.v.) and GHRH (1 micro g/kg, no more than 100 micro g, i.v.) plus ghrelin (1 micro g/kg, no more than 100 micro g, i.v.). Blood samples were taken at appropriate intervals for determination of GH. Statistical analyses were performed by Wilcoxon and by Mann-Whitney tests. RESULTS: After GHRH, the median peak GH secretion in obese patients was 2.4 micro g/l (range 0.9-8.9 micro g/l). Ghrelin-induced GH secretion showed in obese patients a median peak of 24.4 micro g/l (range 7.4-85.0 micro g/l), significantly greater than the response after GHRH (P < 0.05). After the combined administration of GHRH plus ghrelin in obese patients the median peak GH secretion was 39.9 micro g/l (range 19.2-120.0 micro g/l), significantly greater than the response after GHRH (P < 0.05) or ghrelin (P < 0.05). GHRH-induced GH secretion in normal control subjects showed a median peak of 25.0 micro g/l (range 16.5-33.4 micro g/l). Ghrelin-induced GH secretion in normal showed a median peak of 68.5 micro g/l (range 22.5-119.5 micro g/l), significantly greater than the response after GHRH (P < 0.05). After the combined administration of GHRH plus ghrelin, in normal subjects the median peak GH secretion was 117.8 micro g/l (range 77.5-280.1 micro g/l), significantly greater than the response after GHRH or ghrelin alone (P < 0.05). When we compare the response of normal and obese patients, after GHRH alone, it was markedly decreased in obese people when compared with normal patients (P < 0.05) with a median GH peak of 25.0 micro g/l (range 16.5-33.4 micro g/l) and 2.4 micro g/l (range 0.9-8.9 micro g/l) for normal and obese patients, respectively. When we compare the response of normal and obese patients, after ghrelin alone or GHRH plus ghrelin, it was only blunted in obese subjects when compared with normal subjects with a median GH peak of 68.5 micro g/l (range 22.5-119.5 micro g/l) and 24.4 micro g/l (range 7.4-85 micro g/l) for normal and obese subjects, respectively, after ghrelin alone (P < 0.05) and a median GH peak of 117.8 micro g/l (range 77.5-280.1 micro g/l) and 39.9 micro g/l (range 19.2-120.0 micro g/l) for normal and obese patients, respectively, after GHRH plus ghrelin (P < 0.05). CONCLUSIONS: This study has demonstrated a massive GH response to ghrelin alone or combined with GHRH in obese patients, suggesting that altered ghrelin secretion could play a major role in the blunted GH secretion present in obese patients.

Comparison between insulin tolerance test, growth hormone (GH)-releasing hormone (GHRH), GHRH plus acipimox and GHRH plus GH-releasing peptide-6 for the diagnosis of adult GH deficiency in normal subjects, obese and hypopituitary patients.

OBJECTIVE: It has been gradually realized that GH may have important physiological functions in adult humans. The biochemical diagnosis of adult GHD is established by provocative testing of GH secretion. The insulin-tolerance test (ITT) is the best validated. The ITT has been challenged because of its low degree of reproducibility and lack of normal range, and is contra-indicated in common clinical situations. Furthermore, in severely obese subjects the response to the ITT frequently overlaps with those found in non-obese adult patients with GHD. DESIGN: The aim of the present study was to evaluate the diagnostic capability of four different stimuli of GH secretion: ITT, GHRH, GHRH plus acipimox (GHRH+Ac), and GHRH plus GHRP-6 (GHRH+GHRP-6), in two pathophysiological situations: hypopituitarism and obesity, and normal subjects. METHODS: Eight adults with hypopituitarism (four female, four male) aged 41-62 Years (48.8+/-1.4 Years), ten obese normal patients (five female, five male) aged 38-62 Years (48.1+/-2.5 Years), with a body mass index of 34.2+/-1.2 kg/m(2), and ten normal subjects (five female, five male) aged 33-62 Years (48.1+/-2.8 Years) were studied. Four tests were performed on each patient or normal subject: An ITT (0.1 U/kg, 0.15 U/kg for obese, i.v., 0 min), GHRH (100 microg, i.v., 0 min), GHRH (100 microg, i.v., 0 min) preceded by acipimox (250 mg, orally, at -270 min and -60 min) (GHRH+Ac); and GHRH (100 microg, i.v., 0 min) plus GHRP-6 (100 microg, i.v., 0 min) (GHRH+GHRP-6). Serum GH was measured by radioimmunoassay. Statistical analyses were performed by Wilcoxon rank sum and by Mann-Whitney tests. RESULTS: After the ITT the mean peak GH secretion was 1.5+/-0.3 microg/l for hypopituitary, 10.1+/-1.7 microg/l (P<0.05 vs hypopituitary) for obese and 17.8+/-2.0 microg/l (P<0.05 vs hypopituitary) for normal. GHRH-induced GH secretion was 2+/-0.7 microg/l for hypopituitary, 3.9+/-1.2 microg/l (P=NS vs hypopituitary) for obese and 22.2+/-3.8 microg/l (P<0.05 vs hypopituitary) for normal. After GHRH+Ac, mean peak GH secretion was 3.3+/-1.4 microg/l for hypopituitary, 14.2+/-2.7 microg/l (P<0.05 vs hypopituitary) for obese and 35.1+/-5.2 microg/l (P<0.05 vs hypopituitary) for normal. GHRH+GHRP-6 induced mean peak GH secretion of 4.1+/-0.9 microg/l for hypopituitary, 38.5+/-6.5 microg/l (P<0.05 vs hypopituitary) for obese and 68.1+/-5.5 microg/l (P<0.05 vs hypopituitary) for normal subjects. Individually considered, after ITT, GHRH or GHRH+Ac, the maximal response in hypopituitary patients was lower than the minimal response in normal but higher than the minimal response in obese subjects. In contrast, after GHRH+GHRP-6 the maximal response in hypopituitary patients was lower than the minimal response in normal and obese subjects. CONCLUSIONS: This study suggests that, in this group of patients, although both acipimox and GHRP-6 partially reverse the functional hyposomamotropism of obesity after GHRH, but are unable to reverse the organic hyposomatotropism of hypopituitarism, the combined test GHRH+GHRP-6 most accurately distinguishes both situations, without the side effects of ITT.